The research focuses on three related areas--triggering of endplate channel opening by acetylcholine and other agonists, generation of miniature endplate currents, and interaction of molecules with the channel. In the first area the experiments will test the hypothesis that channel opening is triggered by a concerted rate limiting receptor conformation change following with variable probability on the independent binding of agonist molecules to equivalent receptor sites. The main tool is concentration dependence of noise parameters in a large frequency range, though determination of binding site stoichiometry and spontaneously open channel number is also planned. A specific hypothesis for miniature endplate current generation will also be tested, using bungarotoxin, anticholinesterases and voltage jumps, in relation to the kinetic data for acetylcholine from noise experiments. The structure of the channel will be probed using local anesthetic-like agents and permeant ions. In all three areas, the combined voltage clamp-focal recording technique will be extensively used.